It is difficult to lose weight. It is even more difficult to maintain weight loss. In the past few years, it has become clear why this is so: energy intake, energy expenditure, and body weight are all centrally regulated by the hypothalamus.[1] We are beginning to understand this regulatory system. Neuropeptide Y and agouti-related protein stimulate appetite and are inhibited by leptin, which circulates in proportion to body adiposity. Many other peptides, such as alpha-melanocyte-stimulating hormone, cholecystokinin, ghrelin, peptide YY, insulin, and a host of others -- some probably not yet described -- are involved in energy homeostasis. The regulatory system appears to be both complex and redundant with fail-safe features. Thus, when we ask patients to restrict energy intake and increase energy expenditure through exercise to lose weight, we are asking them to override a powerful biological control system. This is something most people simply cannot do.

Health Benefits of Weight Loss for Diabetes Patients

If overweight patients with type 2 diabetes are able to lose weight, they can expect substantial health benefits, including improvements in glycemia, lipemia, and blood pressure. In a weight-loss study[2] that my colleagues and I recently completed, the relationship between weight loss at 1 year and hemoglobin A1C (A1C) in type 2 diabetic subjects was A1C change = 0.11 (weight change in kg) + 0.18. Thus, if a type 2 diabetic subject loses 5 kg (11 lbs) in 1 year, he or she can expect a decrement in A1C of 0.4% (-0.4 = 0.11 [-5] + 0.18). This probably underestimates the effect of weight loss because, without intervention, one would expect a type 2 diabetes patient to demonstrate a modest increment in A1C after 1 year. Thus, weight loss is highly desirable for most patients with type 2 diabetes.

Facts and Fads

How to help people with type 2 diabetes lose weight is a more difficult issue. As pointed out in the most recent American Diabetes Association (ADA) nutrition recommendations, standard weight reduction diets (diets with 500-1000 kcal fewer per day than estimated to be necessary for weight maintenance) simply do not work when used alone.[3] Rather, one must employ an intensive program in lifestyle modification such as was used in the Diabetes Prevention Program (DPP).[4] The DPP provided a structured lifestyle modification program that included a low-calorie, low-fat diet; increased moderate-intensity physical activity; one-on-one educational sessions; and frequent contact with healthcare providers. With this intervention, participants were able to lose 7% of their body weight in the first year and maintain a 5% weight loss over the 3-year follow-up period. This reduced the incidence of diabetes in persons at high risk by 58%.

In view of current dietary fads, the weight-loss approach used in the DPP deserves further discussion. The initial approach to weight loss was a reduction in dietary fat intake so that it comprises less than 25% of calories consumed, which is consistent with the nutrition recommendations for weight loss made by the ADA and also suggests that dietary fat is the most important nutrient to restrict.[3] Restricting dietary fat is at odds with the currently popular Atkins diet, which is low in carbohydrate, high in protein, and high in fat. Which of these approaches is better is not yet clear.

In a recently published 1-year trial comparing a high-carbohydrate, low-fat, conventional weight loss diet with a low-carbohydrate, high-protein, high-fat, Atkins-like diet, the Atkins-like diet produced greater weight loss than did the conventional diet at 6 months (7.0% vs 3.2% reduction in body weight).[5] However, the difference between the diets was not significant at 1 year, and participant attrition was high in both diet groups. Thus, long-term adherence to an Atkins-like diet is difficult, and is perhaps related to its monotony. Other fad diets, such as the South Beach Diet, have not been studied in carefully conducted clinical trials but presumably would not have greater efficacy than the Atkins diet for the same reason.)

Meal Replacements

Another weight-loss approach employed in the DPP was the use of meal replacements such as Slim Fast. This approach has become an important part of the weight-loss strategy in Action for Health in Diabetes (LookAHEAD).[6] LookAHEAD is a multicenter clinical trial sponsored by the National Institutes of Health that is examining weight loss as a strategy for the prevention of cardiovascular disease in people with type 2 diabetes. Once- or twice-daily use of meal replacements has become a key part of the weight-loss program. Use of meal replacements was first demonstrated to be effective by Ditschuneit and co-investigators.[7] This group demonstrated that use of Slim Fast products to replace 1 or 2 meals daily in overweight subjects resulted in the loss of 11% of starting weight at 27 months. The meal-replacement products provided 220 calories derived from carbohydrate and protein and also supplied vitamins, minerals, and fiber. By using such products to replace a meal, the caloric intake at that meal is reduced. The efficacy of meal-replacement products appears to be good in selected subjects, and safety and cost are not significant concerns.

Weight-Loss Medications

Weight-loss medications may also be considered in the treatment of patients with type 2 diabetes. Fenfluramine and phentermine were effective in producing weight loss and improvements in glycemia in type 2 diabetic subjects,[8] but fenfluramine was removed from the market in the United States because of an association with valvular heart disease and can thus no longer be employed. Sibutramine, which acts centrally to reduce appetite, produced weight loss of 5.5 kg and a modest decrement in A1C at 12 months in type 2 diabetic subjects,[9] but may produce increases in pulse rate and blood pressure as side effects. When used in combination with meal replacements and intermittent low-calorie diets, sibutramine produced a decrement in weight of 7.3 kg and a reduction in A1C of 0.6% at 1 year in type 2 diabetic subjects.[2] Orlistat, which interferes with pancreatic lipase and causes malabsorption of a portion of dietary fat, produced weight loss of 4% to 6% of starting weight at 1 year in 3 different studies of subjects with type 2 diabetes.[10-12] In all 3 studies, the weight loss produced by orlistat resulted in modest improvements in glycemia. Thus, currently available weight-loss medications produce modest but clinically significant weight loss and modest reductions in glycemia in diabetic subjects. However, weight-loss medications are expensive and must be continued indefinitely to maintain weight loss.

Bariatric Surgery

The ultimate approach to weight loss for patients with type 2 diabetes is probably surgical. A variety of bariatric surgical procedures are available, but the best studied is gastric bypass. In one series of 397 obese patients who underwent gastric bypass, mean weight loss at 18 months was 52 kg (115 lbs), and the weight loss was well maintained for 6 years.[13] Eighty-eight people enrolled in the trial had diabetes mellitus; all but 2 became euglycemic without further need for diabetes medication. There were 3 perioperative deaths (0.8% of subjects). Surgical complications (primarily wound infections) sufficient to delay hospital discharge occurred in 11% of subjects. However, long-term data comparing surgical and medical therapies for obesity in patients with type 2 diabetes are not available. It has been recommended that bariatric surgery be considered in patients with type 2 diabetes only when body mass index (BMI) exceeds 35 kg/m2.[14] Of note, gastric bypass surgery can now be done laparoscopically, which appears to reduce morbidity and shorten hospital stays.

Summary

Weight loss is an important but difficult therapeutic objective for people with type 2 diabetes. The best dietary weight-loss strategy has not been defined, and all such strategies are compromised by the body's potent methods of maintaining energy homeostasis and defeating weight loss. The ADA currently recommends a reduced-fat diet as part of a structured program of lifestyle change for weight loss. Daily use of meal replacements can be an effective strategy for some people but must be continued long term if weight loss is to be maintained. Currently available weight-loss medications have modest efficacy but also must be continued long term if weight loss is to be maintained. More effective weight-loss medications will probably become available in the future as the biochemistry of energy balance becomes better understood and new pharmacologic tools are developed. Gastric bypass surgery is currently the most effective long-term weight-loss strategy, but this approach has not been compared with medical therapies for patients with type 2 diabetes and should be reserved for those with type 2 diabetes and BMI > 35 kg/m2.

References

Korner J, Leibel RL. To eat or not to eat  how the gut talks to the brain. N Engl J Med. 2003;349:926-928. Abstract